【结 构 式】 |
【分子编号】23569 【品名】(1R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene 【CA登记号】 |
【 分 子 式 】C10H16 【 分 子 量 】136.23704 【元素组成】C 88.16% H 11.84% |
合成路线1
该中间体在本合成路线中的序号:(I)A) Synthesis of intermediate (IX): The reaction of alpha-pinene (I) with paraformaldehyde at 180 C gives 10-hydroxymethyl-2-pinene (II), which by reaction with dihydropyran and p-toluenesulfonic acid in dichloromethane is converted to the tetrahydropyranyl ether (III) The reaction of (III) with diborane in THF affords 10-(tetra-hydropyran-2yloxymethyl)pinan-3-ol (IV), which is oxidized with CrO3 - MnSO4 - H2SO4 in ether to the ketone (V). The stereoselective reduction of (V) with NaBH4 in methanol gives the alcohol (VI), which is mesylated with methanesulfonyl chloride and triethylamine in dichloromethane to the mesyl ester (VII). The reaction of (VII) with sodium azide in HMPT yields the azide (VIII), which by reduction with LiAlH4 in refluxing ethyl ether affords 10-tetrahydropyran-2-yloxymethyl)pinan-3-ylamine (IX).
【1】 Kawasaki, A.; Miyake, H.; Okegawa, T. (Ono Pharmaceutical Co., Ltd.); 13-Aza-14-oxo-TXA2 analogues. AU 8543495; EP 0171146; ES 8704880; ES 8705370; JP 1989151545; US 4792550 . |
【2】 Castaner, J.; Prous, J.; ONO-3708. Drugs Fut 1987, 12, 5, 446. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 23569 | (1R,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene | C10H16 | 详情 | 详情 | |
(II) | 23570 | 2-[(1S,5R)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]-1-ethanol | C11H18O | 详情 | 详情 | |
(III) | 23571 | 2-[3-[(1S,5R)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]propoxy]tetrahydro-2H-pyran; 3-[(1S,5R)-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl]propyl tetrahydro-2H-pyran-2-yl ether | C17H28O2 | 详情 | 详情 | |
(IV) | 23572 | (1S,2S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]heptan-3-ol | C17H30O3 | 详情 | 详情 | |
(V) | 23573 | (1S,2S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]heptan-3-one | C17H28O3 | 详情 | 详情 | |
(VI) | 23574 | (1S,2S,3R,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]heptan-3-ol | C17H30O3 | 详情 | 详情 | |
(VII) | 23575 | 2-[3-((1S,2S,3R,5R)-6,6-dimethyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]bicyclo[3.1.1]hept-2-yl)propoxy]tetrahydro-2H-pyran; 3-((1S,2S,3R,5R)-6,6-dimethyl-3-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]bicyclo[3.1.1]hept-2-yl)propyl tetrahydro-2H-pyran-2-yl ether | C20H36O3S | 详情 | 详情 | |
(VIII) | 23576 | 2-[3-[(1S,2S,3S,5R)-3-azido-6,6-dimethylbicyclo[3.1.1]hept-2-yl]propoxy]tetrahydro-2H-pyran; 3-[(1S,2S,3S,5R)-3-azido-6,6-dimethylbicyclo[3.1.1]hept-2-yl]propyl tetrahydro-2H-pyran-2-yl ether | C17H29N3O2 | 详情 | 详情 | |
(IX) | 23577 | (1S,2S,3S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]heptan-3-amine; (1S,2S,3S,5R)-6,6-dimethyl-2-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]bicyclo[3.1.1]hept-3-ylamine | C17H31NO2 | 详情 | 详情 |